Advertisement

Dyslipidemias pp 483-497 | Cite as

Low-Density Lipoprotein (LDL) Apheresis

  • P. Barton DuellEmail author
Chapter
Part of the Contemporary Endocrinology book series (COE)

Abstract

Low-density lipoprotein (LDL) apheresis, also referred to as lipoprotein apheresis or lipid apheresis, is a procedure that involves extracorporeal treatment of plasma to remove apoprotein (apo) B-containing lipoproteins followed by reinfusion of the processed blood. This specialized adjunctive procedure is reserved for patients who have severe refractory hypercholesterolemia after treatment with maximally tolerated LDL-lowering medications in combination with lifestyle changes, most often in the context of the genetic disorder familial hypercholesterolemia (FH). It is estimated that 2–4 % of patients with FH meet the criteria for initiating LDL apheresis, which means that about 1 in 12,500 to 1 in 50,000 individuals may be candidates for LDL apheresis. The approximately 3-h procedure acutely lowers the plasma LDL cholesterol concentration by up to 85 %, as well as lowering the concentrations of Lp(a) and remnant lipoproteins. The procedure has several documented cardiovascular benefits, including a 72 % reduction in cardiovascular events compared to standard medical therapy in a long-term open label trial.

Keywords

LDL apheresis Apoprotein B Low-density lipoprotein (LDL) Lipoprotein(a) Familial hypercholesterolemia Atherosclerosis 

References

  1. 1.
    Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the national lipid association expert panel on familial hypercholesterolemia. J Clin Lipidol. 2011;5:S1–S8.CrossRefPubMedGoogle Scholar
  2. 2.
    Slack J. Risks of ischaemic heart disease in familial hyperlipoproteinemic states. Lancet. 1969;2:1380–82.CrossRefPubMedGoogle Scholar
  3. 3.
    Stone NJ, Levy RI, Fredrickson DS, et al. Coronary artery disease in 116 kindred with familial type II hyperlipoproteinemia. Circulation. 1974;49:476–88.CrossRefPubMedGoogle Scholar
  4. 4.
    Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223(2):262–8CrossRefPubMedGoogle Scholar
  5. 5.
    De Gennes JL Touraine R Maunand B Truffert J Laudat P. Homozygous cutaneo-tendinous forms of hypercholesterolemic xanthomatosis in an exemplary familial case: Trial of plasmapheresis as heroic treatment. Memoires de la Societe Medicale des Hospitaux de Paris. 1967;118:1377–402.Google Scholar
  6. 6.
    Thompson GR, Lowenthal R, Myant R. Plasma exchange in the management of homozygous familial hypercholesterolaemia. Lancet. 1975;1:1208–11.CrossRefPubMedGoogle Scholar
  7. 7.
    Thompson GR, Myant NB, Kilpatrick D, Oakley CM, Raphael MJ, Steiner RE. Assessment of long-term plasma exchange for familial hypercholesterolaemia. Br Heart J. 1980;43:680–8.CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Thompson GR, Miller JP, Breslow JL. Improved survival of patients with homozygous familial hypercholesterolaemia treated by plasma exchange. Br Med J. 1985;291:1671–3.CrossRefGoogle Scholar
  9. 9.
    Lupien PJ, Moorjani S, Awad J. A new approach to the management of familial hypercholesterolaemia: removal of plasma cholesterol based on the principle of affinity chromatography. Lancet. 1976;1:1261–4CrossRefPubMedGoogle Scholar
  10. 10.
    Stoffel W, Demant T. Selective removal of apolipoprotein B-containing serum lipoproteins from blood plasma. Proc. Natl Acad Sci USA. 1981;78(1):611–5.CrossRefGoogle Scholar
  11. 11.
    Stoffel W, Borberg H, Greve V. Application of specific extracorporeal removal of low density lipoprotein in familial hypercholesterolaemia. Lancet. 1981;2:1005–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Antwiller GD, Dau PC, Lobdell DD. Treatment of familial hypercholesterolemia by precipitation of low density lipoproteins with dextran sulfate. In: Proceedings of the 1st International Congress of the World Apher Association; 1985; p. 68Google Scholar
  13. 13.
    Mabuchi H, Michishita I, Takeda M, Fujita H, Koizumi J, Takeda R, Takada S, Oonishi M. A new low density lipoprotein apheresis system using two dextran sulfate cellulose columns in an automated column regenerating unit (LDL continuous apheresis). Atherosclerosis. 1987;68(1–2):19–25.CrossRefPubMedGoogle Scholar
  14. 14.
    Wieland H, Seidel D. A simple specific method for precipitation of low density lipoproteins. J Lipid Res. 1983;24(7):904–9.PubMedGoogle Scholar
  15. 15.
    Eisenhauer T, Armstrong VW, Wieland H, Fuchs C, Scheler F, Seidel D. Selective removal of low density lipoproteins (LDL) by precipitation at low pH: first clinical application of the HELP system. Klin Wochenschr. 1987;65(4):161–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Communication from Patrick Moriarty. Presentation at Cardiometabolic Health Conferency, Boston, MA. October 4, 2013.Google Scholar
  17. 17.
    Ito MK, McGowan MP, Moriarty PM. Management of Familial Hypercholesterolemias in adult patients: recommendations from the national lipid association expert panel on familial hypercholesterolemia. J Clin Lipidol. 2011;5:538–45.Google Scholar
  18. 18.
    Civiera F. for the international panel on management of familial hypercholesterolemia: guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis. 2004;173:55–68.CrossRefGoogle Scholar
  19. 19.
    FDA Summary of safety and probable benefit (SSPB). http://www.accessdata.fda.gov/cdrh_docs/pdf12/H120005b.pdf. Accessed 26 Sept 2014.
  20. 20.
    Jaeger BT, Richter Y, Nagel D, et al. Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nature Clin Pract Cardiovas Med. 2009;6(3):229–39.CrossRefGoogle Scholar
  21. 21.
  22. 22.
    Sorokin A, Brown JL, Thompson PD. Primary biliary cirrhosis, hyperlipidemia, and atherosclerotic risk: a systematic review. Atherosclerosis. 2007;194(2):293.CrossRefPubMedGoogle Scholar
  23. 23.
    Franceschini G, Busnach G, Chiesa G, Sirtori CR. Management of lipoprotein-X accumulation in severe cholestasis by semi-selective LDL-apheresis. Am J Med. 1991;90: 633–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Kobayashi J, Katsube S, Shimoda M, Furuhashi K, Kitano S, Masuda M, Maruyama T, and Shinomiya M. Single LDL apheresis improves serum remnant-like particle-cholesterol, C-reactive protein, and malondialdehyde-modified-low-density lipoprotein concentrations in Japanese hypercholesterolemic subjects. Clinica Chimica Acta. 2002;321:107–12.CrossRefGoogle Scholar
  25. 25.
    Russi G, Furci L, Leonelli M, et al. Lipoprotein glomerulopathy treated with LDL-apheresis (Heparin-induced extracorporeal lipoprotein precipitation system): a case report. J Med Case Reports. 2009;3:9311CrossRefPubMedCentralGoogle Scholar
  26. 26.
    Muso E. Beneficial effect of LDL-apheresis in refractory nephrotic syndrome. Clin Exp Nephrol. 2014;18(2):286–90CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Muso E, Mune M, Fujii Y, Imai E, Ueda N, Hatta K, Imada A, Miki S, Kuwahara T, Takamitsu Y, Takemura T, Tsubakihara Y. Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis treatment (K-FLAT) study group. Kidney Int Suppl. 1999;71:S122–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Muso E, Mune M, Fujii Y, Imai E, Ueda N, Hatta K, Imada A, Takemura T, Miki S, Kuwahara T, Takamitsu Y, Tsubakihara Y (The Kansai FGS LDL Apheresis Treatment (K-FLAT) Study Group). Significantly rapid relief from steroid-resistant nephrotic syndrome by LDL apheresis compared with steroid monotherapy. Nephron. 2001;89(4):408–15.CrossRefPubMedGoogle Scholar
  29. 29.
    Suckfüll M, Thiery J, Schorn K, Kastenbauer E, Seidel D. Clinical utility of LDL-apheresis in the treatment of sudden hearing loss: a prospective, randomized study. Acta Otolaryngol. 1999;119(7):763–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Suckfüll M for the Hearing Loss Study Group. Fibrinogen and LDL apheresis in treatment of sudden hearing loss: a randomised multicentre trial. The Lancet. 2002;360(9348):1811–7.CrossRefGoogle Scholar
  31. 31.
    Heigla F, Hetticha R, Suckfuell M, Luebbersc CW, Osterkornd D, Osterkornd K, Canis M. Fibrinogen/LDL apheresis as successful second-line treatment of sudden hearing loss: a retrospective study on 217 patients. Atherosclerosis Supp. 2009;10(5):95–101.CrossRefGoogle Scholar
  32. 32.
    Canis M, Heigl F, Suckfuell M. Fibrinogen/LDL apheresis is a promising rescue therapy for sudden sensorineural hearing loss. Clin Res Cardiol Suppl. 2012;7(1):36–40.CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Bianchin G, Russi G, Romano N, Fioravanti, P. Treatment with HELP-apheresis in patients suffering from sudden sensorineural hearing loss: a prospective, randomized, controlled study. The Laryngoscope. 2010;120(4):800–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Wanders RJA, Waterham HR, Leroy BP. Refsum Disease. GeneReviews® [Internet]. Initial Posting: March 20, 2006; Last Update: April 22, 2010 (https://www.ncbi.nlm.nih.gov/books/NBK1353/). Accessed 26 Sept 2014.
  35. 35.
    Refsum S. Heredopathica atactica polyneuritiformis: a familial syndrome not hitherto described. Acta Psychiat Scand Suppl. 1946;38:1–303.Google Scholar
  36. 36.
    Steinberg D, Herndon JH, Uhlendorf BW, Mize CE, Avigan J, Milne GWA. Refsum's disease: nature of the enzyme defect. Science. 1967;156:1740–1742.CrossRefPubMedGoogle Scholar
  37. 37.
    Steinberg D, Mize CE, Avigan J, Fales HM, Eldjarn L, Try K, Stokke O, Refsum S. Studies on the metabolic error in Refsum’s disease. J Clin Invest. 1967;46:313–22.CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Steinberg D, Vroom FQ, Engel WK, Cammermeyer J, Mize CE, Avigan J. Refsum’s disease–a recently characterized lipidosis involving the nervous system. Ann. Intern. Med. 1967;66:365–95.CrossRefPubMedGoogle Scholar
  39. 39.
    Steinberg D. Mize CE Herndon JH Fales HM Engel WK Vroom FQ. Phytanic acid in patients with Refsum’s syndrome and response to dietary treatment. Arch Intern Med. 1970;125:75–87.CrossRefPubMedGoogle Scholar
  40. 40.
    Straube R, Gäckler D, Thiele A, Muselmann L, Kingreen H, Klingel R. Membrane differential filtration is safe and effective for the long-term treatment of Refsum syndrome––an update of treatment modalities and pathophysiological cognition. Transfusion and Apheresis Science. 2003;29(1):85–91.CrossRefPubMedGoogle Scholar
  41. 41.
    Kroon AA, vant Hof MA, Demacker PN, et al. The rebound of lipoproteins after LDL apheresis. Kinetics and estimation of mean lipoprotein levels. Atherosclerosis. 2000; 152:519–26.CrossRefPubMedGoogle Scholar
  42. 42.
    Schettler V, Monazahian M, Wieland E, Ramadori G, Grunewald RW, Thomssen R, Müller GA. Reduction of hepatitis C virus load by H.E.L.P.-LDL apheresis. Eur J Clin Invest. 2001;31(2):154–5.CrossRefPubMedGoogle Scholar
  43. 43.
    Marson P, Boschetto R, De Silvestro G, Martini S, Gabelli C, Buoro S, Giordano R, Palù G. Changes in HCV viremia following LDL apheresis in a HCV positive patient with familial hypercholesterolemia. Int J Artif Organs. 1999;22(9):640–4.PubMedGoogle Scholar
  44. 44.
    Tavori H, Giunzioni I, Linton MF, Fazio S. Loss of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) after lipoprotein apheresis. Circ Res. 2013;113:1290–5.CrossRefPubMedCentralPubMedGoogle Scholar
  45. 45.
    Duell PB, Dubuc G, Seidah NG, Davignon J. Clearance of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) by LDL apheresis. Circ Res 2014; in press.Google Scholar
  46. 46.
    Thompson GR, Barbir M, Davies D, et al. (HEART-UK LDL apheresis working group): recommendations for use of LDL apheresis. Atherosclerosis. 2008;198(2):247–55.CrossRefPubMedGoogle Scholar
  47. 47.
    Richter WO, Donner MG, Schwandt P. Three LDL apheresis techniques in treatment of patients with familial hypercholesterolemia: a long-term evaluation. Ther Apher. 1999;3:203–8.CrossRefPubMedGoogle Scholar
  48. 48.
    Agishi T, Kaneko I, Hasuo Y, et al. Double filtration plasmapheresis. Ther Apher. 2000;4:29–33. (Reprinted by permission from Trans Am Soc Artif Intern Organs (1980;26:406–411).Google Scholar
  49. 49.
    Mabuchi H, Koizumi J, Shimizu M, Kajinami K, Miyamoto S, Ueda K, Takegoshi T, and the Hokuriku-FH-LDL-Apheresis Study Group. Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Am J Cardiol. 1998;82:1489–95.CrossRefPubMedGoogle Scholar
  50. 50.
    Eisenhauer T, Armstrong VW, Wieland H, Fuchs C, Scheler F, Seidel D. Selective removal of low density lipoproteins (LDL) by precipitation at low pH; first clinical application of the HELP system. Klin Woch. 1987;65:161–8.CrossRefGoogle Scholar
  51. 51.
    Richter WO, Jacob BG, Ritter MM, Suhler K, Vierneisel K, Schwandt P. Three-year treatment of familial heterozygous hypercholesterolemia by extracorporeal low-density lipoprotein immunoadsorption with polyclonal apolipoprotein B antibodies. Metabolism. 1993;42:888–894.CrossRefPubMedGoogle Scholar
  52. 52.
    Pokrovsky SN, Sussekov AV, Afanasieva OI, et al. Extracorporal immunoadsorption for the specific removal of lipoprotein(a) (Lp(a) apheresis): preliminary clinical data. Chem Phys Lipids. 1994;67/68:323–330.CrossRefPubMedGoogle Scholar
  53. 53.
    Bosch T, Schmidt B, Blumenstein M, Gurland HJ. Lipid apheresis by hemoperfusion: in vitro efficacy and ex vivo biocompatibility of a new low-density lipoprotein adsorber compatible with human whole blood. Artif Organs. 1993;17:640–52.CrossRefPubMedGoogle Scholar
  54. 54.
    Bosch T, Schmidt B, Kleophas W, et al. Clinical efficacy and biocompatibility of the first LDL-adsorber compatible with human blood. Int J Artif Organs. 1995;18:417.Google Scholar
  55. 55.
    Moriarty PM, Gibson CA, Shih J, Matias MS. C-reactive protein and other markers of inflammation among patients undergoing HELP LDL apheresis. Atherosclerosis. 2001;158:495–8.CrossRefPubMedGoogle Scholar
  56. 56.
    Empen K, Otto C, Brodl UC, Parhofer KG. The effects of three different LDL apheresis methods on the plasma concentrations of E-selectin, VCAM-1, and ICAM-1. J Clin Apheresis. 2002;17:38–43.CrossRefPubMedGoogle Scholar
  57. 57.
    Tamai O, Matsuoka H, Itabe H, et al. Single LDL apheresis improves endothelium-dependent vasodilation in hypercholesterolemic humans. Circulation. 1997;95:76–82.CrossRefPubMedGoogle Scholar
  58. 58.
    Stadler RW, Ibrahim SF, Lees RS. Peripheral vasoreactivity in in familial hypercholesterolemic patients treated with heparin-induced extracorporal LDL precipitation (HELP). Atherosclerosis. 1997;128:241–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Mellwig KP, Baller D, Gleichmann U, et al. Improvement of coronary vasodilation capacity through single LDL apheresis. Atherosclerosis. 1998;139:173–8.CrossRefPubMedGoogle Scholar
  60. 60.
    Richter WO, Donner MG, Hofling B, Schwandt P. Long-term effect of low-density lipoprotein apheresis on plasma lipoproteins and coronary heart disease in native vessels and coronary bypass in severe heterozygous familial hypercholesterolemia. Metabolism. 1998;47:863–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Schuff-Werner P. Clinical long-term results of HELP-apheresis. Z Kardiol. 2003;92:III28–9.CrossRefPubMedGoogle Scholar
  62. 62.
    Kroon AA, Aengevaeren WR, van der WT, et al. LDL-apheresis atherosclerosis regression study (LAARS). Effect of aggressive versus conventional lipid-lowering treatment on coronary atherosclerosis. Circulation. 1996;93:1826–35.CrossRefPubMedGoogle Scholar
  63. 63.
    Aengevaeren WR, Kroon AA, Stalenhoef AF, Uijen GJ, van der WT. Low-density lipoprotein apheresis improves regional myocardial perfusion in patients with hypercholesterolemia and extensive coronary artery disease. LDL-apheresis atherosclerosis regression study (LAARS). J Am Coll Cardiol. 1996;28:1696–704.CrossRefPubMedGoogle Scholar
  64. 64.
    Matsuzaki M, Hiramori K, Imaizumi T, et al. Intravascular ultrasound evaluation of coronary plaque regression by low-density lipoprotein apheresis in familial hypercholesterolemia. The Low-density lipoprotein apheresis coronary morphology and reserve trial (LACMART). J Am Coll Cardiol. 2002;40:220–7.CrossRefPubMedGoogle Scholar
  65. 65.
    Nishimura S, Sekiguchi M, Kano T, et al. Effects of intensive lipid lowering by low-density lipoprotein apheresis on regression of coronary atherosclerosis in patients with familial hypercholesterolemia: Japan low-density lipoprotein apheresis coronary atherosclerosis prospective study (L-CAPS). Atherosclerosis. 1999;144:409–17.CrossRefPubMedGoogle Scholar
  66. 66.
    Hoffmann U, Derfler K, Haas M, et al. Effects of combined low-density lipoprotein apheresis and aggressive statin therapy on coronary calcified plaque as measured by computed tomography. Am J Cardiol 2003;91:461–4.CrossRefPubMedGoogle Scholar
  67. 67.
    Koga N, Watanabe K, Kurashige Y, Sato T, Hiroki T. Long-term effects of LDL apheresis on carotid arterial atherosclerosis in familial hypercholesterolaemic patients. J Intern Med. 1999;246:35–43.CrossRefPubMedGoogle Scholar
  68. 68.
    Gordon BR, Kelsey SF, Dau PC, et al. Long-term effects of low density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. Liposorber Study Group. Am J Cardiol. 1998;81:407–11.CrossRefPubMedGoogle Scholar
  69. 69.
    Kutsumi Y, Tada H, Iwamuro A, Kabuto H. Is low-density lipoprotein apheresis effective for coronary artery disease? ASAIO J. 1998;44:M666–9.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press 2015

Authors and Affiliations

  1. 1.Division of Endocrinology, Diabetes, and Clinical NutritionOregon Health and Science UniversityPortlandUSA

Personalised recommendations